The need for systems that can deliver a drug at a controlled rate of release to an environment of use over a specified period of time is well established.
U.S. Pat. Nos. 3,854,770 and 3,916,899 disclose devices which have semipermeable walls that are permeable to water and substantially impermeable to dissolved drugs and solutes. A passageway through the semipermeable wall, disclosed as a drilled hole, is provided as an exit portal for the drug through the wall. U.S. Pat. Nos. 4,256,108; 4,160,452; 4,200,098 and 4,285,987 disclose devices which contain multiple wall layers, at least one of said walls having a drilled hole for the release of core components through a rate-controlling semipermeable membrane that is substantially impermeable to dissolved drugs and other solutes. The use of controlled release solubility modulators that regulate the solubility of the drug(s) within the device to control drug release from the an osmotic drug-delivery device were not disclosed. U.S. Pat. No. 4,326,525 is also based on semipermeable membrane technology with a drilled hole acting as exit portal for the drug. This patent discloses the use of buffers which react via proton-transfer or neutralizing reactions with the drug to produce a new drug agent which has different thermodynamic properties from the parent drug.
U.S. Pat. No. 4,755,180 is also based on semi-permeable membrane technology with a drilled hole acting as the exit portal for the drug. This patent discloses the use of buffers and osmagents to induce control of drug solubility through manipulation of the drug pH/solubility profile or through competition for available water, that is thermodynamic alteration of the water, respectively. In all cases the drug released from the device exits as a free unassociated dissolved molecule that is solvated directly by water. This approach would be ineffective, for example, in manipulation of poorly soluble drugs with no acid/base character.
The usefulness of the above devices would be increased if a device and method were provided to improve the delivery of drugs which have been found to be difficult to incorporate into an osmotic drug delivery module without conversion of the parent drug into a new drug whose stability and toxicology are uncharacterized. Further utility results from methodology which provides for a sustaining of the improvement inducing effect through use of solubility modulating agents that are effective in the formulation of poorly water soluble drugs having no acid/base character in technology which substantially extends the lifetime of the modulating agent(s).